Stereodefined Improbable [3]Rotaxane by Post‐Interlocking Ring Editing

ABSTRACT The synthesis of higher‐order mechanically interlocked molecules is challenging when targeting so‐called improbable rotaxanes—statistically disfavored architectures whose ring and axle components lack mutual recognition. This challenge becomes more severe when the rings are racemic or stereolabile, as any successful assembly will inevitably produce a stereoisomeric mixture rather than a well‐defined product. Herein, we demonstrate a post‐interlocking ring editing strategy using covalent organic pillar COP‐1 as the ring component. Nanotubular COP‐1 is assembled by dynamic covalent imine condensation of two inherently chiral yet stereolabile macrocyclic building blocks that exhibit negligible binding towards long n ‐alkyl threads. Preorganization within COP‐1 renders the duplex scaffold stereostable, enabling its chiral resolution and switching on ring‐axle recognition. Using the resolved CO P ‐1 , a threading‐followed‐by‐stoppering protocol furnishes enantiopure [2]rotaxanes. Subsequent imine hydrolysis edits the interlocked COP‐1 duplex into its two parent macrocycles, converting each [2]rotaxane into the corresponding improbable [3]rotaxane. The mechanical bond preserves the stereochemical configuration inherited from COP‐1 , without loss of enantiopurity. This post‐interlocking ring editing strategy circumvents the statistical limitations of direct multiring interlocking, providing a programmable route to stereodefined improbable rotaxanes and design principles for higher‐order chiral mechanically interlocked architectures.